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Current Pediatric Reviews
ISSN: 1573-3963
Current Pediatric Reviews
Volume 3, Number 1, February 2007
Contents
Editorial Pp. i
RAGE Signaling in Cell Adhesion and Inflammation
Pp. 1-9
Bärbel Lange-Sperandio, Markus Sperandio, Peter Nawroth
and Angelika Bierhaus
[Abstract] [Full
text article]
Hepatitis A Vaccination in Infants: The Ultimate Solution
to a Long-Standing Public Health Problem Pp. 11-19
G. William Letson and Harold S. Margolis
[Abstract] [Full
text article]
Intestinal Microbiota in Neonates and Preterm Infants:
A Review Pp. 21-35
Marie France de La Cochetière, Carole Rougé,
Dominique Darmaun, Jean Christophe Rozé, Gilles Potel
and Christele Gras Leguen
[Abstract] [Full
text article]
Urinary Tract Infection Why Do Some Children Get Complications,
While Others Don’t? Pp. 37-46
Milan Chromek and Annelie Brauner
[Abstract] [Full
text article]
Human Milk has Anti-Oxidant Properties to Protect
Premature Infants Pp. 47-53
Apollinaire Tsopmo and James K. Friel
[Abstract] [Full
text article]
LCHAD and MTP Deficiencies - Two Disorders of Mitochondrial
Fatty Acid β-Oxidation
with Unusual Features Pp. 55-61
Petra Eskelin and Tiina Tyni
[Abstract] [Full
text article]
Fragile X Syndrome and Autism: Common Developmental
Pathways? Pp. 63-70
Kim Cornish, Jeremy Turk and Andrew Levitas
[Abstract] [Full
text article]
Back Pain in the Young: A Review of Studies Conducted
among School Children and University Students Pp.
71-79
Derek R. Smith and Peter A. Leggat
[Abstract] [Full
text article]
Recent Advances in the Pharmacological Treatment of
Pervasive Developmental Disorders Pp. 81-93
Samareh Moussavand and Robert L. Findling
[Abstract] [Full
text article]
Review of Clinical Trials Testing the Effectiveness
of Physician Approaches to Improving Alcohol Education and
Counseling in Adolescent Outpatients Pp. 95-103
Bradley O. Boekeloo and Melinda A. Griffin
[Abstract] [Full
text article]
Abstracts
[Back to top]
Editorial
Antioxidant Properties of Human Milk
Premature birth is associated with a number of adverse sequaelae;
these include bronchopulmonary dysplasia, necrotizing enterocolitis,
intracerebral haemorrhage and retinopathy of prematurity.
It has been suggested that these conditions are the outcome
of “oxygen radical disease” [1] and occur as a
result of oxidative injury. Premature infants often require
high inspired supplemental oxygen concentrations because of
lung disease and severe sepsis. These conditions are associated
with reduced cardiac output and hypotension, which may lead
to hypoxemia of the tissues. This can result in the generation
of oxygen derived free radicals (reactive oxygen species (ROS)).
To defend against the actions of ROS, there are antioxidants
such as ascorbic acid (vitamin C) and tocopherol (Vitamin
E) and enzymatic defenses such as super oxide dismutase (SOD),
glutathionine peroxidase and catalase. Unfortunately, the
premature infant has poor antioxidant defense mechanisms.
In this issue of the journal Tsopmo and Friel [2] report data
from a literature review to highlight that human milk has
antioxidant properties. In particular, they note that human
milk contains vitamins C and E and enzymes including superoxide
dismutase, catalase and glutathione peroxidase. Human milk
is often frozen and stored for deferred use for very prematurely
born and sick infants. Freezing decreases the antioxidant
activity of milk in a time dependent fashion [3], but the
antioxidant activity of human milk, despite storage, is still
higher than that of infant formulae. This may at least partially
explain why prematurely born infants fed with breast milk
rather than cow’s milk based infant formulae have a
lower incidence of nectrotising enterocolitis [4] and retinopathy
of prematurity [5].
REFERENCES
[1] Saugstadt OD. Oxygen toxicity in the neonatal period.
Acta Pediatr Scand 1990; 79: 881-92.
[2] Tsopmo A, Friel JK. Human milk has anti-oxidant properties
to protect premature infants. Curr Ped Rev 2007; 3: 47-54.
[3] Hanna N, Ahmed K, Anwar M, Petrova A, Hiatt M, Hegyi T.
Effect of storage on breast milk antioxidant activity. Arch
Dis Child Fetal Neonatal Ed 2004; 89: F518-20.
[4] Lucas A, Cole TJ. Breast milk and necrotizing enterocolitis.
Lancet 1990; 336: 1519-23.
[5] Cunningham AS. Breast feeding, antioxidants and the retinopathy
of prematurity. Am J Obstet Gynecol 1987; 156: 1040-1.
Prof. Anne Greenough
King’s College London, MRC-Asthma Centre
Division of Asthma, Allergy and Lung Biology
King’s College Hospital, Denmark Hill
London, SE5 9RS
UK
E-mail: anne.greenough@kcl.ac.uk
[Back to top]
RAGE Signaling in Cell Adhesion and Inflammation
Bärbel Lange-Sperandio, Markus Sperandio, Peter Nawroth
and Angelika Bierhaus
[Full
text article]
The receptor for advanced glycation endproducts (RAGE) has
been shown to play an important role in aging, neurodegeneration,
diabetes, and inflammation. RAGE is a transmembrane receptor
of the immunoglobuline superfamily, which recognizes a variety
of ligands such as AGEs (advanced glycation endproducts),
members of the S100/calgranulin family of proinflammatory
mediators, β-sheet-fibrills,
HMGB1 (amphoterin) and the β2-integrin
Mac-1. RAGE/ligand interactions induce oxidative stress and
lead to an up-regulation of pro-inflammatory pathways involving
the proinflammatory transcription factor NF-κB,
increased expression of cytokines, chemokines, and adhesion
molecules. These effects markedly propagate cellular dysfunction
and cause perturbation in a diverse group of diseases, such
as age-related neurodegenerative disorders, atherosclerosis,
diabetic vascular complications, tumors, and chronic inflammatory
disease. In addition, RAGE may also interfere with differentiation
processes, which are required during organ development. In
this article, we have reviewed recent advances on RAGE and
RAGE/ligand function in cell adhesion and inflammation based
on findings from cell cultures, animal models, and human diseases.
The potential for targeting the RAGE/ligand pathway as therapeutic
strategy will be discussed.
[Back to top]
Hepatitis A Vaccination in Infants: The Ultimate Solution
to a Long-Standing Public Health Problem
G. William Letson and Harold S. Margolis
[Full
text article]
Infection with hepatitis A virus (HAV) is common in children.
Among children < 5 years of age, <10% present with jaundice
and manifest HAV infection with diarrhea, nausea, vomiting,
malaise or no visible signs or symptoms. Prior to introduction
of hepatitis A vaccine in the United States, the reported
incidence of symptomatic disease was highest among children
5 to 14 years of age (15.6/100,000), however, seroprevalence
data indicated that children <5 years of age had the highest
infection incidence (637.4/100,000). The significance of these
finding is that young children with asymptomatic infection
act as silent reservoirs for HAV transmission within the community.
Hepatitis A immunization provides long-term immunity against
HAV infection and early childhood immunization has been shown
to halt HAV transmission in communities with previously high
incidence of disease. Incorporation of hepatitis A vaccine
into the early childhood immunization schedule was impeded
by the finding that passively acquired maternal antibody significantly
inhibited immunogenicity of vaccine administered during infancy.
However, recent studies have shown that little passively acquired
antibody remains early in the second year of life and does
not interfere with vaccine immunogenicity. Early childhood
hepatitis A vaccination has significantly lowered disease
incidence in a number of populations, worldwide. Among vaccinated
and unvaccinated children, there has been a > 85% reduction
in disease incidence and a 69-90% reduction in disease incidence
among unvaccinated adults in the same populations. The effectiveness
and cost-effectiveness of childhood hepatitis A vaccination
combined with no increase in adverse events among more than
2.3 million vaccinated children has led to recent recommendations
that hepatitis A vaccine be incorporated into the early childhood
immunization schedule in the United States.
[Back to top]
Intestinal Microbiota in Neonates and Preterm Infants:
A Review
Marie France de La Cochetière, Carole Rougé,
Dominique Darmaun, Jean Christophe Rozé, Gilles Potel
and Christele Gras Leguen
[Full
text article]
The fetal gastrointestinal tract is sterile until birth when
microbes colonize the gastrointestinal tract, and a dense,
complex microbiota develops. This enormous cell mass performs
a variety of activities that affect both the intestinal and
systemic physiology. The microbiota provides nutritional,
metabolic, immunological, and protective functions. The neonatal
gastrointestinal tract is an organ at risk. Increasing awareness
that the human flora is a major factor in both health and
disease has led to different strategies to manipulate the
flora. Manipulation with prebiotics and probiotics has shown
promising results although a better understanding of the gut
bacterial colonization process is required before attempts
to change the flora should be made. In this review, we summarize
the data regarding developmental microbial ecology in the
neonatal gastrointestinal tract, and the modulation of such
microbiota. The discussion focuses on the control and manipulation
of bacterial colonization in the neonatal gut for the prevention
and treatment of bacterial intestinal disease in both in human
infants and on animal models. Since the best available methodologies
should be utilized in studies of nutritional sciences, a recapitulation
of the latest techniques for the study of the gastrointestinal
flora is presented. Future progress is likely to arise from
the use of genomic techniques to track of diet-induced changes
in microbiota.
[Back to top]
Urinary Tract Infection Why Do Some Children Get Complications,
While Others Don’t?
Milan Chromek and Annelie Brauner
[Full
text article]
Urinary tract infection, one of the commonest bacterial diseases
in children, carries a substantial risk of serious complications.
Amongst them, renal scarring and recurrent infections seem
to be the most important. In this review, we analyze the pathogenesis
of urinary tract infection in order to identify those children
who run the highest risk of unfavorable outcome. During infection,
multiple bacterial and host factors interact with each other.
Bacteria possess specific characteristics involved in the
process of adhesion, invasion, survival and host damage during
infection. Host factors also substantially participate in
the pathogenesis of the disease. According to current knowledge,
the specific host response appears to be the main factor predisposing
for complications. However, prompt and adequate treatment
of acute urinary tract infection remains the most important
measure to prevent scarring. Dysfunctional holding and elimination
of urine, on the other hand, mainly seem to influence the
development of recurrent infection. Despite intensive research
for many years, urinary tract infections are still a challenge
for patients and health care professionals.
[Back to top]
Human Milk has Anti-Oxidant Properties to Protect
Premature Infants
Apollinaire Tsopmo and James K. Friel
[Full
text article]
Human milk (HM) is recognized as the optimal form of nutrition
in the newborn period, providing nutrients and a variety of
components (minerals, vitamins, enzymes, hormones, growth
factors, and immunoglobulins) that are very important for
growth and healthy development. In the case of premature (PM)
infants, functional and in certain cases, structural development
of most organ systems is completed in the weeks following
birth. PM infants do not get enough oxygen and may require
supplemental oxygen as high as 95%. This high level of inspired
oxygen necessary to maintain arterial oxygen tension exposes
these infants to more reactive oxygen species (ROS) compared
with full term infants. ROS may lead to diseases associated
with prematurity, including necrotizing enterocolitis, retinopathy
of prematurity, intraventricular-periventricular hemorrhage,
and bronchopulmonary dysplasia. There is then a need to reduce
oxidative stress or boost antioxidant defenses in these vulnerable
infants. Data suggest that HM has unique antioxidant properties
that will assist the premature infant in coping with the increased
oxidative stress. HM antioxidant components include the enzymes
superoxide dismutase for dismutation of superoxide anion,
catalase for degradation of hydrogen peroxide (H2O2),
glutathione peroxidase for destruction of H2O2
and organic peroxides. Human milk contains other molecules
including cysteine, vitamins C and E, which are scavengers
of oxygen radicals.
[Back to top]
LCHAD and MTP Deficiencies - Two Disorders of Mitochondrial
Fatty Acid β-Oxidation
with Unusual Features
Petra Eskelin and Tiina Tyni
[Full
text article]
Mitochondrial fatty acid β-oxidation
disorders are relatively common causes of acute metabolic
crises and sudden death in infants. Most of these disorders
can be treated effectively, provided, fasting is avoided and
there is an early start of a high-carbohydrate low-fat diet
therapy. Two disorders, long-chain 3-hydroxyacyl-CoA dehydrogenase
(LCHAD) and complete mitochondrial trifunctional protein (MTP)
deficiencies, have pathogenetically interesting and therapeutically
challenging manifestations, which are atypical of β-oxidation
defects. In addition to the classical manifestations of disorders
affecting β-oxidation
of long-chain fatty acids (hypoketotic hypoglycaemia, hepatopathy,
cardiomyopathy and rhabdomyolysis), patients with LCHAD and
MTP defects have pigmentary retinopathy, which causes visual
handicap, progressive peripheral neuropathy and hypoparathyreosis.
Furthermore, female carriers may have devastating pre-eclampsia-related
complications and in particular acute fatty liver during pregnancy.
Pathogenesis research of the important characteristic features
of LCHAD and MTP deficiencies would not only improve opportunities
for new therapeutic strategies but could increase our understanding
of tissue metabolism affected by these disorders.
[Back to top]
Fragile X Syndrome and Autism: Common Developmental
Pathways?
Kim Cornish, Jeremy Turk and Andrew Levitas
[Full
text article]
Identifying atypical trajectories that distinguish children
with differing developmental disorders from each other and
from typically developing children is a potentially powerful
tool for early ascertainment and treatment of syndrome specific
proficiencies and deficiencies. The past decade has seen unparalleled
advances in the fields of molecular genetics, pediatrics,
developmental cognitive neuroscience and brain imaging. Collaboratively,
these advances have facilitated our understanding of how genes
can impact upon early development, through the identification
of specific patterns of cognitive and behavior processing
and the deficits in these domains that are typical to a specific
developmental disorder. These advances have also made early
diagnoses possible for many developmental disorders, including
those for which genetic etiology has yet to be determined,
such as is the case for most individuals with autism, or disorders
such as fragile X syndrome that result from the silencing
of a single gene. This early identification necessitates thorough
investigation of the impact of a condition across the lifespan
beginning in early childhood when interventions are most likely
to have significant benefit. This is especially relevant for
disorders that at first glance appear to share overlapping
behavioral and clinical symptomology. In the case of autism
and fragile X syndrome, commonalties in social and communication
profiles are now well documented in early childhood. However,
to what degree symptom overlap implies common developmental
pathways or etiologies remains unclear. The focus of this
review will be to critically evaluate whether so called ‘commonalities’
in phenotypic outcomes actually reflect very different developmental
pathways that diverge over developmental time and across syndromes.
More detailed knowledge of these profiles will facilitate
early timing of tailored interventions that will promote optimal
development resulting in significant educational, clinical,
and adaptive benefits across a child’s lifespan.
[Back to top]
Back Pain in the Young: A Review of Studies Conducted
among School Children and University Students
Derek R. Smith and Peter A. Leggat
[Full
text article]
Back Pain [BP] represents one of the most common occupational
disorders among human beings, with almost all people experiencing
it at some stage during their life. Despite the well-known
relationships between workplace factors and BP among adults,
BP also affects younger people, such as school children and
university students. Although some evidence suggests an increasing
prevalence of BP throughout later childhood, it is difficult
to ascertain whether this reflects a true increase in prevalence,
or just greater recognition of the problem by researchers
and research subjects. Nevertheless, various studies have
begun to highlight a variety of BP risk factors in young people,
such as classroom posture, backpacks, computer usage and psychosocial
factors. As today’s school children and university students
may be a generation increasingly burdened by BP, it is essential
that clinicians in the paediatric field keep abreast of contemporary
issues and risks, so that they may more effectively deal with
this growing menace.
[Back to top]
Recent Advances in the Pharmacological Treatment of
Pervasive Developmental Disorders
Samareh Moussavand and Robert L. Findling
[Full
text article]
Introduction. There is growing body of evidence to
suggest that pharmacotherapy may be a rational form of intervention
for some patients with pervasive developmental disorders (PDDs).
The purpose of this article is to describe what is known about
medication treatment for these patients.
Methods. Published papers regarding the pharmacotherapy
of PDDs were collected and reviewed. For each study, particular
attention was paid to ascertaining patient characteristics,
the medication doses employed, and medication tolerability.
Results. There is evidence of varying methodological
rigor to suggest that several medications may have a role
in the treatment of patients with PDDs. However, to date,
few randomized double-blind treatment studies have been published.
In addition, there is very little known about the long-term
safety of many of these agents in this patient population.
Conclusions. Some patients with PDDs may benefit
acutely from pharmacotherapy. Many marketed psychotropic agents
that putatively hold promise for these patients have not been
rigorously studied. More short-term and long-term research
regarding the pharmacotherapy of patients with PDDs is needed.
[Back to top]
Review of Clinical Trials Testing the Effectiveness
of Physician Approaches to Improving Alcohol Education and
Counseling in Adolescent Outpatients
Bradley O. Boekeloo and Melinda A. Griffin
[Full
text article]
Objective: Conduct a review of clinical
trials to identify effective approaches for improving physician
provision of alcohol education and counseling services among
outpatient adolescents.
Methods: Reviewed all peer-reviewed,
published clinical trials identified through computerized
searches evaluating alcohol education and counseling services
to outpatient adolescents by physicians.
Results: Three trials were identified
examining changes in physician provision of alcohol education
and counseling services. One of the trials resulted in increased
adolescent self-reported refusal skills, while another trial
resulted in reduction of adolescent self-reported alcohol
use and binge drinking. Seven trials were identified that
compared physician with non-physician provision of alcohol
education and counseling services. Four of the trials showed
some reduction in adolescent self-reported alcohol use.
Conclusion: Trials indicate that
further reduction in adolescent alcohol use is possible with
non-physicians as interventionists and perhaps physicians
as interventionists, if physicians are supported by patient
counseling guides and resources. Opportunities for personalized,
interactive adolescent education with goal setting appears
key to intervention success. The physician role that is tested
in most trials is confined to a single brief encounter with
little attention to: development of physician skills, systems-level
resources, the parental role, or the impact of incorporating
prevention into an ongoing adolescent-physician relationship.
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